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Biomedical subjects

R D Catalano

Publications and source records attributed to R D Catalano.

10 recordsLinked to original sources
PubMed2006

Identification of novel genes regulated by chorionic gonadotropin in baboon endometrium during the window of implantation.

Chorionic gonadotropin (CG) is an early embryo-derived signal that is known to support the corpus luteum. An in vivo baboon model was used to study the direct actions of human CG (hCG) on the endometrium, during the periimplantation period. Endometrial gene expression was analyzed using microarrays. The endometrial biopsies were taken from hCG-treated (n = 5) and control (n = 6) animals on d 10 after ovulation. Class comparison identified 61 genes whose transcript levels differed between control and hCG-treated samples (48 increased, 13 decreased in mean expression level more than 2.5-fold; P < 0.01). Real-time PCR of transcript abundance confirmed up-regulation of several of these, including SerpinA3, matrix metalloproteinase 7, leukemia inhibitory factor (LIF), IL-6, and Complement 3 (P </= 0.05). Analysis of protein abundance in endometrial flushings showed increased LIF and IL-6 protein in uterine flushings from hCG-treated animals compared with controls. Complement C3 and Superoxide dismutase 2 that were also up-regulated, were further evaluated by immunocytochemistry. Complement C3 showed a marked increase in stromal staining in response to hCG, whereas and superoxide dismutase 2 localization was most markedly increased in the glandular epithelial cells. Expression of Soluble Frizzled Related Protein 4, the most highly down-regulated gene, was also validated by PCR. Our experiments have shown that hCG induces alterations in the endometrial expression of genes that regulate embryo attachment, extracellular matrix remodeling and the modulation of the immune response around the implanting blastocyst. Several of these genes, including LIF and gp130, have been shown to be essential for implantation in other species. This study provides strong evidence that the preimplantation embryo itself influences the development of the receptive endometrium via secreted paracrine signals.

Animals↗
PubMed2006

Temporal expression profiling of the uterine luminal epithelium of the pseudo-pregnant mouse suggests receptivity to the fertilized egg is associated with complex transcriptional changes.

BACKGROUND: The molecular basis of changes underlying the altered sensitivity of the uterine luminal epithelium (LE) to the embryo over the peri-implantation period is not fully understood. METHODS: Microarray analysis was performed on purified LE isolated from the pseudo-pregnant mouse uterus at 12-h intervals from pre-receptivity through the implantation window to refractoriness. The aim was to identify genes whose expression changes in the LE during this period. RESULTS: A total of 447 transcripts were identified whose abundance changed more than 2-fold in the LE but which did not change in the underlying stroma (S) and glands. Six major patterns of changing expression were noted. Of the 447 genes, 140 were expressed in LE at least 15-fold higher than in S and glandular epithelium (GE) (101 of these more than 20-fold). Detailed spatiotemporal expression profiles were derived for several genes previously implicated in implantation (including Edg7, Ptgs1, Pla2g4a and Alox15). CONCLUSIONS: Functional changes in LE receptivity are characterized by changing constellations of gene expression. Pre-receptivity has a different molecular footprint to refractoriness. Because we have used the pseudo-pregnant mouse model, these changes are driven solely by endocrine signals rather than events downstream of embryo attachment. Some of these genes have been described in previous microarray studies on endometrium, but for the majority, this is the first time they have been implicated in implantation. The 140 genes enriched in the LE greatly expand the list of epithelial markers and provide many novel candidates for further studies to identify genes playing important roles in receptivity and embryo attachment.

Animals↗
PubMed2006

Effect of an intrauterine device on the gene expression profile of the endometrium.

CONTEXT: The human endometrium acquires the ability to allow embryo attachment just for a specific period of time during each menstrual cycle. Understanding of the opposite functional status, referred to as refractoriness, can potentially be used to improve receptivity in infertile patients or as an interceptive approach to prevent gestation. OBJECTIVE: The objective of the study was to analyze the endometrial gene expression profile induced by an inert intrauterine device (IUD) at the time of implantation. DESIGN: We used a microarray containing more than 16,000 cDNAs to investigate the gene expression profile of receptive vs. refractory endometrium in the same women induced by the presence of an IUD. We compared the gene expression profile of endometrium obtained at LH+7 (window of receptivity) from the same women (n = 5) at the following time points: month 1, corresponding to the natural cycle before IUD insertion; month 3, just before IUD removal; and months 5 and 15. Data were validated by quantitative RT-PCR for IGF binding protein-3, peroxisome proliferative activated receptor-gamma, glycodelin, and leukemia inhibitory factor and immunohistochemistry for glycodelin. RESULTS: We identified 147 genes significantly dysregulated in the refractory endometrium (78 up- and 69 down-regulated). Interestingly, 52 of these genes have previously been reported to be regulated during window of implantation. Surprisingly, the majority of genes (96.6%) remained dysregulated 2 months after IUD removal, but 1 yr later most of them (80%) returned to normal. CONCLUSIONS: Our results reveal that a refractory endometrium in a fertile woman produced by an IUD is induced by preventing the normal transition to a receptive gene expression profile through effects on a specific subset or cluster of genes that impact on endometrial receptivity.

Adult↗
PubMed2003

The effect of RU486 on the gene expression profile in an endometrial explant model.

Administration of RU486 in vivo during the receptive phase rapidly renders the endometrium non-receptive to the implanting embryo. In order to identify key pathways responsible for endometrial receptivity we have used cDNA arrays to monitor gene expression changes in short-term endometrial explants in response to RU486. Endometrial biopsies from five normal fertile women at mid-secretory phase were cultured in the presence of estradiol and progesterone with or without RU486 for 12 h. cDNA arrays were produced containing approximately 1000 sequence-verified clones which included genes known to be important in angiogenesis, apoptosis, cell signalling, extracellular matrix remodelling and cell cycle regulation. cDNA probes from the paired endometrial samples were hybridized to the arrays and hybridization signals were quantified. A total of 12 genes displayed significant changes in expression; six were up-regulated and six down-regulated following RU486 treatment. For five of these genes this is the first report suggesting that they are regulated by steroids in the endometrium. JAK1 and JNK1 were two of the genes shown by the arrays to be down-regulated in RU486-treated endometrial explants. This was confirmed by real time RT-PCR. JAK1 immunoreactivity was localized to both glandular epithelium and the stroma of normal endometrium and staining was much stronger in the luteal phase of the cycle. These results show that components of two important signalling pathways in endometrium-the JAK/STAT pathway, and the JNK pathway-are altered by RU486. Genes whose expression is controlled by these pathways are likely to be involved in the mechanism by which steroids render the endometrium receptive to the implanting embryo.

Adult↗
PubMed2001

Developmental expression and characterization of FS39, a testis complementary DNA encoding an intermediate filament-related protein of the sperm fibrous sheath.

Proteins immunologically related to intermediate filaments have been identified in the sperm fibrous sheath but remain uncharacterized. We isolated and characterized a novel intermediate filament-related protein (FS39) localized to the fibrous sheath of the sperm tail. We used Northern blot analysis to establish that FS39 is transcribed predominantly in the testis of mice >18-20 days old. At this age, spermatogenesis has proceeded to the development of the first round haploid spermatids. In situ hybridization revealed that FS39 mRNA is first detectable in late step 3 spermatids, is at its highest level during steps 9 and 10, and diminishes in steps 13 and 14. Western blot analysis identified a single protein of 39 kDa in mouse and rat testis and epididymis, suggesting the protein is conserved in rodents. Indirect immunofluorescence localized FS39 to the fibrous sheath of the sperm tail, and in testis sections expression was detected from step 13 and step 14 spermatids onward, indicating FS39 is under translational control. Southern blot analysis showed FS39 to be a single copy gene, and hybridization to human genomic DNA suggested that a human equivalent gene is present. These results demonstrate that FS39 is transcribed in testis tissue during the haploid phase of spermatogenesis, is present in mature sperm, and codes for a novel 39-kDa intermediate filament-related protein of the fibrous sheath.

Amino Acid Sequence↗
PubMed1997

Differential display to identify and isolate novel genes expressed during spermatogenesis.

Spermatogenesis is a complex differentiation process in which diverse stage-specific proteins are co-ordinately expressed. Previously, subtractive hybridization and differential hybridization have been used in the identification of differentially expressed mRNAs. Although these techniques have been successfully used they require large amounts of RNA and are time consuming. To overcome these problems we have made use of the recently described mRNA differential display technique. The technique is an effective method which can identify and separate cDNAs that are differentially expressed between various cell-types. By comparing RNA from testes of mature (> 60 days old) and prepubertal (15-16 days old) mice we have identified nine differential cDNA bands expressed in mature testes. The differential display cDNA band DDC8 was used screen a testis cDNA library and the full length cDNA was isolated and sequenced. DDC8 cDNA is 1965 bp with an open reading frame of 533 amino acids which codes for a predicated hydrophilic protein with a calculated molecular weight of 62.04 kDa. RNase protection assays indicate DDC8 to be expressed during the postmeiotic stages of spermatogenesis and database searches using both nucleotide and amino acid sequences show DDC8 to have similarities to structural, cytoskeletal and associated proteins.

Amino Acid Sequence↗
PubMed1997

Angiography in blunt thoracic aortic injury.

PURPOSE: Recent studies have suggested that transesophageal echocardiography (TEE) can be used as the primary imaging method in patients suspected of traumatic rupture of the thoracic aorta. A segment of the aorta and the aortic arch branches cannot be adequately evaluated in all patients by TEE. To assess the impact of these limitations of TEE, this retrospective study examined the aortographic features of traumatic aortic or great vessel injuries in a large number of patients. MATERIALS AND METHODS: We retrospectively reviewed clinical and imaging features of 89 patients with a history of blunt chest trauma and angiographic evidence of traumatic injury to the thoracic aorta or to its branches. RESULTS: Of these 89 patients, 72 had aortic rupture alone. One (1%) of these ruptures occurred at the distal ascending aorta, a potential blind spot for TEE. Seventeen patients (19%) had 24 injuries to the aortic arch branches: in 14 of these 17 patients, the aorta was intact, whereas three patients also had aortic rupture. Seventy percent of the injuries to the aortic arch branches were not suspected on physical examination. CONCLUSION: Twenty percent of patients in our retrospective series had traumatic involvement of aortic arch branches or the distal ascending aorta. These vascular injuries may be suboptimally assessed or overlooked if TEE is used as the sole imaging modality in the evaluation of patients with blunt chest trauma.

Adolescent↗
PubMed1986

Characterization of corticotropin receptors in human adrenocortical cells.

[125I-Tyr23,Phe2,Nle4]ACTH-(1-38) ([125I]ACTH analog), which is equipotent with ACTH, was used to characterize ACTH receptors in human adrenocortical cells. Adrenals were obtained from brain-dead patients at the time of renal harvest with permission. Binding of [125I]ACTH analog to human adrenocortical cells was highly specific, rapid, reversible, and saturable. Analysis of the inhibition of binding of [125I]ACTH analog by ACTH was compatible with a single class of binding sites with an apparent dissociation constant (Kd) of 1.6 nM and a mean binding capacity of 3560 sites/cell. Concentration-response curves for cAMP and cortisol production were shifted to the left of the binding curve, with ACTH concentrations required for half-maximal stimulation being 20- and 720-fold less, respectively, than those for binding. Extracellular calcium was essential for binding and stimulation of cAMP production. These results indicate that human adrenocortical cells contain a single class of ACTH receptors which are highly similar in affinity, capacity, and calcium requirement to those of rat adrenocortical cells, but differ from the rat receptors in the concentration of ACTH needed for cAMP generation.

Adrenal Cortex↗
PubMed1984

Mechanisms of adrenocortical depression during Escherichia coli shock.

The response of the adrenal cortex to corticotropin during sepsis is variable. We have previously demonstrated a significant decrease of corticosterone production by rat adrenocortical cells in response to corticotropin stimulation after incubation with septic shock plasma (SP) as compared with control plasma (CP). We have studied the mechanisms of this depression. The following defects were demonstrated. (1) Cells bound less radioiodinated corticotropin analog after SP treatment (2.9 +/- 0.4 femtomoles/50 micrograms DNA) than after CP treatment (6.4 +/- 0.3 fmole/50 micrograms DNA). (2) Cyclic adenosine monophosphate (cAMP) production was less after SP treatment (59.3 +/- 4 pmole per 10(5) cells per two hours) compared with CP treatment (110.3 +/- 11.3 pmole per 10(5) cells per two hours). (3) Exogenously added dibutyryl cAMP was unable to correct the defect in corticosterone production after SP treatment (4.96 +/- 0.7 micrograms/24 hr) as compared with CP treatment (6.99 +/- 0.5 micrograms/24 hr). Our studies suggest this defect is located in the synthesis of pregnenolone from cholesterol. These mechanisms may be responsible for the low cortisol levels previously observed in humans during septic shock.

Adrenal Cortex↗